1. Field of the Invention
The present invention relates to a method for carrying out an iron-catalyzed allylic alkylation and its use.
2. The Prior Art
In the synthesis of natural products or of pharmacologically interesting compounds, various methods are being developed in synthetic organic chemistry that permit the construction of chiral structures. Numerous methods have been developed to increase activity and selectivity. Among them, for example, are racemate resolution via reversible derivatization with chiral auxiliaries followed by separation, the use of enantiomerically pure starting materials, the use of chiral auxiliaries in stoichiometric reactions, or the use of reactions in the presence of a chiral catalyst.
Among the most important catalytic reactions in organic chemistry for forming carbon-carbon bonds is transition metal-catalyzed allylic alkylation. In this reaction, an allyl complex that reacts with a nucleophile is generated by oxidative addition of a transition metal complex to an allyl substrate. The transition metal is reduced again, and the reaction product is liberated.
However, the preparation of allylically highly substituted carbon structural units represents a central problem of preparative synthetic organic chemistry, because alkylation usually occurs on the less highly substituted carbon. An attack on the sterically favored unsubstituted allyl terminus would lead to the unwanted linear isomer. Therefore, it is of special interest to steer the attack to the more highly substituted allyl end.
Numerous transition metals can be used to cause carbon-nucleophiles to react selectively with allylically activated substrates, wherein the organic parts of the allyl-metal fragments formed can be considered formally as carbocation equivalents. The methods so far known for metal-catalyzed allylic alkylation using palladium, nickel, iridium, rhodium, or similar metals, pass through the formation of intermediate metal-allyl complexes. Among the best-known and most powerful methods developed is asymmetric palladium-catalyzed allylic alkylation by the method of TROST et al. Numerous reviews provide a good survey of its research and application.
Intermediate (π-allyl)metal complexes are formed in transition metal catalysis, that do offer advantages with regard to possible stereoinduction by chiral ligands, but frequently lead to the formation of regioisomeric mixtures in the case of an unsymetrically substituted substrate. Because of this formation, it is often impossible to achieve control of regioselectivity of the alkylation at the differently substituted termini of the allyl fragment.
This frequently undesired side effect can be partially lessened by the use of ligands. Some of the systems do lead to enrichment of the higher branching products that are poorly accessible, but the regioselectivities are unsatisfactory at best.
High regioselectivities play a large role in natural product synthesis (for example, in the synthesis of carbohydrates). Therefore, a need exists for a method for selective allylic alkylations in which the new carbon-carbon bond can be constructed on the carbon that has previously been substituted with the nucleofug.
Furthermore, the catalysts disclosed by the state of the art, most of which contain noble metals, are distinguished by high prices and by their sensitivity to oxygen and water. Such reactions as a rule have to be carried out with strict exclusion of oxygen and water, which from the industrial viewpoint is directly associated with additional costs for equipment. The transition metals used are also toxic, which is particularly troublesome from economic and ecological viewpoints. Workup and disposal of toxic catalysts means additional costs from the necessary safety measures and purification steps.
The development of nontoxic, economical catalysts that are distinguished by a high degree of regioselectivity in allylic alkylation is therefore of great synthetic interest.
Another catalyst that can be used for allylic alkylation is known from the state of the art. As early as 1979, Roustan published the synthesis of an iron complex that catalyzes allylic alkylation. This system was later refined by Zhou by the use of the formal Fe(-II) complex [Bu4N] [Fe(CO)3(NO)] (appeared in 1987). Both catalyst systems are distinguished by a high catalyst load. The allylic alkylation here does not occur with the development of a (π-allyl)metal species.
This Fe(-II) complex was not developed further because of the poor reproducibility of results and the deficient description of the preparation of the active catalyst. The reaction also is carried out there under a toxic CO atmosphere. Handling carbon monoxide is likewise disadvantageous, so that in this case no further scientific research was pursued.